Adolescence is a peak time for the onset of mental illnesses, with anxiety being the most common disorder and affecting as many as 1 in 10 youth. A core feature of anxiety disorders is difficulty identifying when situations that have been experienced as threatening in the past are currently safe. Despite substantial changes in the neural circuitry supporting emotion regulation and fear extinction across development, interventions for youth are largely based on treatment principles studied and implemented in adulthood. The primary goal of this application is to investigate the efficacy of safety signal learning as a novel method of fear reduction targeting the biological state of the developing brain. Rodent studies have shown that safety signals effectively reduce anxiety to treat and prevent the development of new fears. This learning relies largely on the hippocampus, a region that shows significant development from childhood to adolescence. Yet safety signal learning remains largely unexplored in humans, especially during adolescence when anxiety peaks. The proposed research adapts a paradigm used in animal studies to test the efficacy of safety signals across development in healthy children and adolescents and those with anxiety disorders. Aim 1 will examine the normative development of safety signal learning and related hippocampal-frontoamygdala circuitry across childhood and adolescence. Aim 2 will test safety signal learning for reducing fear among anxious children and adolescents and test the hypothesis that hippocampal-frontoamygdala circuitry deviates from typical development in these individuals. Aim 3 will examine how type and severity of anxiety relate to safety signal learning and hippocampal- frontoamygdala development. Understanding these neurodevelopmental changes and the roles that they play in both the emergence of illness onset and in treatment efficacy is critical to alleviating the high psychological and economic burden that psychiatric disorders have on the individual and on society. This project is expected to have direct implications for the timing and types of intervention for child and adolescent anxiety, fillng a large gap in the current literature.